Three fairly distinct projects in which electro-optical techniques will be used to investigate the processes of excitability and E-C coupling in heart muscle are proposed. I. The electro-optical signal obtained from merocyanine rhodamine or merocyanine oxazole stained hearts will be used not only to monitor the adequacy of the voltage clamp technique but to use it in the feedback loop of the voltage clamp system. Such rapid optical voltage clamp system will make it possible to homogeneously clamp the membrane during the upstroke and plateau and study the kinetics of Ca 2 ion and Na currents without complications arising from extracellular resistance and spinal inhomogeneity. II. Permeable or impermeable dyes will be used to study the activity of the sarcoplasmic reticulum (SR) in the cardiac muscle. The techniques of chemical skinning and cut end procedure and liposome loading will be used to introduce nonpermeant dyes with high S/N ratio into the cell. Our preliminary experiments using Nile Blue A and indocarboxyanine dyes have not been successful because the signal is distorted by mechanical motion of the muscle. A new technique is proposed to length clamp a small segment of the muscle using a constant pressure device. The response of the SR during a cardiac cycle will be monitored under conditions of ion, drug and frequency intervention. III. Electrosensitive dye, merocyanine-rhodamine will be used to map the active conduction pathways in the heart. Two acousto-optical deflectors will be used to scan a light beam from a laser across the surface of the heart muscle. The reflected light is detected by a photodiode and the signal digitalized for computer recognition. The scanning system can position the laser beam anywhere in a field of 40 x 40 spots within 2 micron seconds. The spot size will be varied from 0.2 mm to 1.0 cm depending on geometry and the space constant of the preparation. A high speed processor will lock the laser beam on the electrical wave front. The technique will be used to map the spread of electricity in normal and injured myocardium.